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Intrastriatal Injection of Autologous Blood or Clostridial Collagenase as Murine Models of Intracerebral Hemorrhage
Published on: July 3, 2014
Caveolin-1 deletion reduces early brain injury after experimental intracerebral hemorrhage
Che-Feng Chang1, Shu-Fen Chen, Tzong-Shyuan Lee
1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Insights
Caveolin-1 (Cav-1) exacerbates early brain injury following intracerebral hemorrhage (ICH). Inhibiting Cav-1 may offer a new therapeutic strategy for hemorrhagic stroke treatment.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Intracerebral hemorrhage (ICH) is a severe stroke subtype with high mortality.
- Caveolin-1 (Cav-1), a key structural protein in caveolae, regulates cellular signaling and cholesterol transport.
- The role of Cav-1 in ICH pathogenesis is currently unknown.
Purpose of the Study:
- To investigate the function of Cav-1 in a mouse model of ICH and in neuronal cultures.
- To determine whether Cav-1 plays a protective or detrimental role in early brain injury after ICH.
Main Methods:
- Utilized collagenase-induced ICH model in Cav-1 knockout and wild-type mice.
- Examined Cav-1 expression in perihematomal brain tissue and neuronal cultures.
- Assessed neurological deficits, brain edema, neuronal death, leukocyte infiltration, inflammatory mediators (MIP-2, COX-2), MMP-9 activity, HO-1 expression, and reactive oxygen species (ROS) production.
- Investigated neuronal vulnerability to hemin-induced toxicity in vitro.
Main Results:
- Cav-1 expression was upregulated in the perihematomal area, particularly in endothelial cells.
- Cav-1 knockout mice exhibited reduced injury volume, milder neurological deficits, less brain edema, and decreased neuronal death compared to wild-type mice.
- Deletion of Cav-1 suppressed leukocyte infiltration, inflammatory mediator expression, MMP-9 activity, HO-1 induction, and ROS production.
- Cav-1 deficiency reduced neuronal vulnerability to hemin toxicity in vitro.
Conclusions:
- Cav-1 plays a detrimental role in early brain injury following ICH.
- Targeting Cav-1 presents a potential novel therapeutic strategy for treating hemorrhagic stroke.
Abstract:
Intracerebral hemorrhage (ICH) is a subtype of stroke with high rates of morbidity and mortality. Caveolin-1 (Cav-1) is the main structural protein of caveolae and is involved in regulating signal transduction and cholesterol trafficking in cells. Although a recent study suggests a protective role of Cav-1 in cerebral ischemia, its function in ICH remains unknown. In this study, we examined the role of Cav-1 and in a model of collagenase-induced ICH and in neuronal cultures. Our results indicate that Cav-1 was up-regulated in the perihematomal area predominantly in endothelial cells. Cav-1 knockout mice had smaller injury volumes, milder neurologic deficits, less brain edema, and neuronal death 1 day after ICH than wild-type mice. The protective mechanism in Cav-1 knockout mice was associated with marked reduction in leukocyte infiltration, decreased expression of inflammatory mediators, including macrophage inflammatory protein (MIP)-2 and cyclooxygenase (COX)-2, and reduced matrix metalloproteinase-9 activity. Deletion of Cav-1 also suppressed heme oxygenase-1 expression and attenuated reactive oxygen species production after ICH. Moreover, deletion or knockdown of Cav-1 decreased neuronal vulnerability to hemin-induced toxicity and reduced heme oxygenase (HO)-1 induction in vitro. These data suggest that Cav-1 plays a deleterious role in early brain injury after ICH. Inhibition of Cav-1 may provide a novel therapeutic approach for the treatment of hemorrhagic stroke.
